Method for providing a circuit for biological liquid and circuit obtained

ABSTRACT

The method comprises the step of forming pipes ( 12 ) by clamping a bag between shells ( 13, 14 ) and by injecting an inflating agent via an inflating connector. 
     The circuit comprises a bag ( 126 ) and a press ( 10 ) comprising two shells ( 13, 14 ) clamping said bag in a state in which pipes ( 12 ) are formed between the films ( 25, 26 ) of the bag.

PRIORITY CLAIMED

French patent application No. 0950435 filed on Jan. 23, 2009.

The invention relates to circuits for biological liquid, in particular,but not exclusively, for purifying a biopharmaceutical liquid in orderto obtain a product such as monoclonal antibodies, vaccines orrecombinant proteins.

It is known that biopharmaceutical liquids are in general obtained byculture in a bioreactor and that they must then be treated to achievethe required characteristics of purity, concentration, absence ofviruses, etc.

These treatments are conventionally carried out in dedicatedinstallations, with stainless steel pipes and other components such astanks and filter housings, which necessitate operations before and afterthe actual treatment, which are relatively onerous, in particularoperations of cleaning after use.

Within the last few years, these treatments have alternatively beencarried out in installations in which the components in contact with theliquid are single-use components.

Such single-use components have the advantage of avoiding cleaningoperations, but, to provide the required degree of security, theimplementation of an installation with such components necessitatesoperations of selection, assembly and verification which are relativelycomplex.

This is especially the case when the number of pipes and other circuitcomponents (connectors, valves, etc.) is high and/or when the operatingpressure is high.

According to a first aspect, the invention aims to provide a circuit forbiological liquid that is particularly simple, convenient and reliable.

To that end, it provides a method for providing a circuit for biologicalliquid comprising a plurality of connectors and a network for routingliquid between said connectors, characterized in that it comprises:

-   -   the step of obtaining a bag comprising two flexible films        attached together by a seal delimiting a closed contour with,        open on the inside and on the outside of said contour, said        routing network connectors and an inflating connector;    -   the step of obtaining a press comprising two shells adapted to        cooperate with said bag to form, between said films, by clamping        said bag between said shells and by injecting an inflating agent        via said inflating connector, pipes of said routing network;        said bag and said press being selected in order for at least one        said pipe to have a contour of which at least one portion is        delimited exclusively by cooperation with said press; and    -   the step of forming said pipes by clamping said bag between said        shells and by injecting an inflating agent via said inflating        connector.

In the circuit provided by the method according to the invention, thepipes of the fluid routing network are not pre-formed, or in any eventnot totally pre-formed, at the initial state of the bag that is used. Onthe contrary, at least one pipe has a contour of which at least oneportion is exclusively delimited by cooperation with the press.

On the bag used, in the initial state, the routing network connectorsopen into the same space, within the bag, surrounded by the seal with aclosed contour.

Due to the fact that the inflating connector opens into the same space,the injection of the inflating agent by that connector enables inflationof that space, provided that this agent cannot escape by the otherconnectors.

By virtue of this inflation, the films can press against the faces ofthe shells with which they are in contact, including the parts of thosefaces which are recessed (the parts which serve for the shaping of thepipes).

The clamping of the bag between the shells enables the contact zonesbetween the films bordering the pipes formed to be made fluid-tight.

As explained later, the inflation may be carried out before the clampingof the bag, after the clamping of the bag, or partially before andpartially after the clamping of the bag.

Once the step of clamping the bag between the shells and of injecting aninflating agent by the inflating connector has been carried out, thecircuit is ready to be placed in service.

This may for example be performed by removing the plugs obturating therouting network connectors (if such plugs were used to enable theinflation of the pipes with the inflating agent) and by connecting thoseconnectors to different containers for liquid, such as a sourcecontainer of liquid to treat and a collecting container for treatedliquid. The connections with the containers are made by simple tubingand/or by sections of more complex circuit comprising for example apump.

Of course, in use, the bag remains clamped between the shells.

In the method according to the invention there is no step of providingconventional tube sets and connectors which must be preassembled.

The circuit obtained by the method according to the invention at thesame time provides the integral character conferred by shaping it from abag, the disposable character of a bag and the character of stiffnessand strength of the shells.

Furthermore, the fact of shaping the pipes of the circuit with theshells which clamp the bag when the circuit is in use, provides,relative to the solution of shaping the pipes beforehand in a separatemanufacturing mold, the advantage of simplifying the manufacturing ofthe bag and the advantage of eliminating the risks from undesirablestresses in the films of the bag when the circuit is in use, whichstresses could have existed due to the differences in shaping, linked tothe manufacturing tolerances, between the manufacturing mold and theshells of the press for the circuit.

According to preferred features of the method according to theinvention:

-   -   said inflating connector is separate from said routing network        connectors;    -   said inflating agent is pneumatic;    -   said step of forming said pipes comprises the step of injecting        an inflating agent before the step of clamping said bag between        said shells; and/or    -   said step of injecting an inflating agent is preceded by a step        of pre-closing said press in which said bag is in immediate        proximity to each of the two shells.

According to a second aspect, the invention also concerns the circuitobtained by the method set forth above.

To that end it provides a circuit for biological liquid which is capableof being obtained by the method as described above, comprising aplurality of connectors and a network for routing liquid between saidconnectors, characterized in that this it comprises:

-   -   a bag comprising two flexible films attached together by a seal        delimiting a closed contour with, open on the inside and on the        outside of said contour, said routing network connectors and an        inflating connector; and    -   a press comprising two shells clamping said bag in a state in        which are formed, between said films, pipes of said network for        routing liquid, inflated by an inflating agent, at least one        said pipe having a contour of which at least one portion is        delimited exclusively by cooperation with said press.

According to preferred features:

-   -   each said shell comprises a shaping channel for each said pipe;    -   each said shaping channel is of semi-circular cross-section;    -   at least one said shell comprises a shaping channel for each        said pipe, with each said shaping channel being bordered on each        side by a groove in which is accommodated a respective bead of a        network of beads serving to apply said films against each other        along said pipes;    -   at least one said shell comprises means for welding said films        along said pipes;    -   the circuit comprises at least one filter enclosed in said bag;    -   at least one said shell comprises at least one actuator of a        pinch valve of a said pipe; and/or    -   at least one said shell comprises at least one sensor of a        physico-chemical value.

The disclosure of the invention will now be continued with the detaileddescription of embodiments, given below by way of illustrative andnon-limiting example, with reference to the accompanying drawings, inwhich:

FIG. 1 is a diagram of a first embodiment of a press and a of bagenabling a circuit in accordance with the invention to be obtained, thebag resting on the lower shell of the press;

FIG. 2 is a similar diagram to FIG. 1, but in which the shells of thepress clamp the bag, in a state in which the circuit is ready to beplaced in service;

FIG. 3 is a similar view to FIG. 1, for a variant of the firstembodiment of the press in which resistors are provided for welding thetwo films of the bag;

FIG. 4 is a relatively detailed perspective view of the shells of asecond embodiment of a press enabling a circuit in accordance with theinvention to be implemented;

FIG. 5 is a perspective view of the bag of that circuit, in its statewhen the circuit is ready to be placed in service;

FIG. 6 is a diagram of the circuit which the shells and the bagillustrated in FIGS. 4 and 5 enable to be obtained;

FIG. 7 is a perspective view of the lower shell of FIG. 4, showing itsface intended to be in contact with the bag;

FIG. 8 is a perspective view of a network of beads provided to be placedin grooves of the face of the lower shell of FIG. 4 that is intended tobe in contact with the bag;

FIG. 9 is a perspective view of the upper shell of FIG. 4, showing itsface intended to be in contact with the bag;

FIGS. 10 and 11 are respectively a perspective view and a plan view of avariant of the lower shell shown in FIGS. 4 and 7, in which only therecesses for implementing the network for routing liquid and foraccommodating the connectors of the bag are represented (to simplify,the other details such as the apertures for the valves and the sensorsor such as the positioning bosses and cavities are not illustrated);

FIG. 12 is an elevation view from the side which can be seen on the leftin FIG. 11;

FIG. 13 is the section view on XIII-XIII of FIG. 11;

FIGS. 14 to 16 are similar views to FIGS. 10 to 12, but for the uppershell;

FIGS. 17 and 18 are section views on XVII-XVII and XVIII-XVIII of FIG.15; and

FIG. 19 is an enlargement of the detail identified by XIX in FIG. 18.

The press 10 and the bag 11 illustrated in FIGS. 1 and 2 make itpossible to obtain a circuit for processing a biological liquidcomprising a plurality of connectors for liquid (which connectors arenot illustrated but are similar to the connectors 40A to 40E of the bag111 of FIG. 5) and a network for routing liquid between thoseconnectors. Some of the pipes 12 of that network can be seen in FIG. 2.

The press 10 comprises two shells 13 and 14.

The shells 13 and 14 are each formed from a sold block of stiffmaterial. Here, the shells 13 and 14 are of stainless steel and are eachof generally parallelepiped shape.

Shell 13 has a reference surface 15, which is planar here, and aplurality of channels 16 recessed into surface 15.

In the same way, shell 14 has a reference surface 17 which is planarhere and channels 18 recessed relative to surface 17, with surfaces 15and 17 being of similar dimensions and the arrangement of the channels18 being the mirror image of the arrangement of the channels 16.

Channels 16 and 18 are of semi-circular cross-section.

The surfaces 15 and 17 may thus be applied against each other with thechannels 16 and 18 in register with each other to delimit a network ofcavities which are each generally tubular.

In addition to the shells 13 and 14, the press 10 comprises, hereimplanted on shell 14, actuators 20 of pinch valves and sensors 21 of aphysico-chemical value, for example pressure or temperature.

The actuators 20 each comprise a body 22 attached to shell 14 and amoveable finger able to adopt a working position and a retractedposition. In the working position, the moveable finger projects from oneof the channels 18.

Each sensor 21 comprises a body 23 attached to shell 14 in register witha channel 18, with the distal end of the body 23 opening into thatchannel 18.

Bag 11 comprises two flexible films 25 and 26 attached to each other bya seal 27 delimiting a closed contour.

Here, each of the films 25 and 26 is a PureFlex™ film from theapplicant. This is a co-extruded film comprising four layers,respectively, from the inside to the outside, a layer of ultra lowdensity polyethylene (ULDPE) forming the material for contact with theliquid, a copolymer of ethylene and vinyl alcohol (EVOH) forming abarrier to gases, a copolymer layer of ethylene and vinyl acetate (EVA)and a layer of ultra low density polyethylene (ULDPE) forming the outerlayers.

The seal 27 is a weld bead formed at the periphery of the films 25 and26.

In addition to films 25 and 26 and connectors for liquid, bag 11comprises a connector for a pneumatic agent (not illustrated, butsimilar to connector 41 of bag 111 in FIG. 5).

The dimensions of bag 11 correspond to those of the reference surfaces15 and 17 of the shells 13 and 14.

Bag 11 is intended to be clamped by shells 13 and 14 with one of thefaces of bag 11 in contact with the face 30 of shell 13 (this facehaving surface 15 and channels 16), and with the other face of bag 11being in contact with face 31 of shell 14 (this face having surface 17and channels 18).

FIG. 1 shows bag 11 in place between shells 13 and 14, here with bag 11resting on face 30 and shell 14 away from bag 11.

Shell 14 is then brought towards shell 13, until surface 17 is incontact or practically in contact with bag 11, but without shells 13 and14 being pressed against each other (pre-closing position).

Bag 11 is then inflated: the connectors for liquid are obturated and apneumatic agent is injected by the connector provided for that purpose.

The effect of inflating bag 11 is that films 25 and 26 respectivelyconforms to face 30 of shell 13 and face 31 of shell 14.

The press 10 is then closed, that is to say that shells 13 and 14 arestrongly pressed against each other while sandwiching the bag 11 (closedposition in which bag 11 is clamped between shells 13 and 14).

Films 25 and 26 are then pressed against faces 30 and 31, including atchannels 16 and 18 where they form the pipes 12, as shown in FIG. 2.

The press 10 and the bag 11 then form a circuit for treating abiological liquid which is ready to be placed in service.

Each actuator 20 enables a pipe 12 to be pinched between its moveablefinger and shell 13, to allow or prevent the passage of the liquid atthat location.

The sensors 21 have their distal end (the sensitive end) in contact witha pipe 12. Each sensor 21 makes it possible to know a physico-chemicalcharacteristic of the liquid flowing in pipe 12 with which its distalend is in contact, for example its temperature or its pressure withouthaving to actually touch the fluid. Such sensors are well known andinclude for example pressure sensors that measure pressure via the outersurface of the bag.

When the biological liquid to process in the circuit formed by press 10and bag 11 has to be protected from contaminations, bag 11 is providedwith obturating plugs in place on each of the connectors for liquid andon the connector for a pneumatic agent and it is sterilized, for exampleby gamma irradiation. The pneumatic agent injected inside bag 11 ispurified. For instance, the pneumatic agent is compressed air purifiedthrough an hydrophobic filter such as an AERVENT® available from thecompany Millipore connected to the inflation connector.

FIG. 3 shows a variant 10′ of press 10, in which shell 13 is replaced bya shell 13′ identical to shell 13 apart from it comprising a heatingdevice 35 such as an electrical resistor, to weld the films 25 and 26 onrespective opposite sides of the pipes 12 in order to make thedelimitation of the pipes 12 permanent. Of course, the welding iscarried out in closed position of the press.

With the aid of FIGS. 4 to 9 a description will now be given of a secondembodiment of a press and of a bag to obtain a circuit in accordancewith the invention.

For similar parts the same numerical references have been kept as onFIGS. 1 and 2, to which 100 has been added.

Whereas in press 10 or 10′ (FIGS. 1 to 3), the actuators 20 and thesensors 21 are implanted on the same shell, in press 110 of theembodiment of FIGS. 4 to 9, the actuators 120A to 120G are implanted onone of the shells (here shell 114) and the sensors 121A to 121D on theother shell (here shell 113).

As can be seen more particularly in FIG. 5, bag 111 comprises fiveconnectors 40A to 40E for liquid and one connector 41 for a pneumaticagent.

In the initial state of bag 111, none of the pipes 112A to 112F has beenformed. The connectors 40A to 40E then each appear as connector 41,which is the only one not to be associated with a liquid routing networkpipe at the time of the shaping of bag 111 by the press 110.

Films 125 and 126 which form bag 111 are each rectangular and of thesame dimensions. They are attached to each other by a peripheral seal127, here a weld in the form of a weld bead extending parallel to theedge of the films, except in the corners where the internal limit of theweld is oblique. In each corner, an opening 42 is formed, here with aright-angle triangle contour, which is surrounded by the weld 127.

It will be noted that the connectors for liquid 40A to 40E and theconnector 41 for a pneumatic agent all open on the inside and on theoutside of the closed contour delimited by the weld 127.

Within the contour delimited by weld 127, bag 111 encloses two filters43 and 44 disposed between the films 125 and 126 at predeterminedlocations, each of the filters 43 and 44 being attached to those films,here by welding.

In the initial state of bag 111, filters 43 and 44 comprise, at each ofthe locations where they are to be connected to a pipe for liquid, a endpiece for interfacing with that pipe.

To accommodate filters 43 and 44, each of the shells 113 and 114 has acorresponding cavity, respectively 43A, 44A in shell 113 and 43B, 44B inshell 114.

Channels 116A to 116F of shell 113 and channels 118A to 118F of shell114 are provided to shape pipes 112A to 112F respectively on bag 111.

Each of the channels 116A to 116F and 118A to 118F is capable ofaccommodating at its corresponding end or ends one of the connectors 40Ato 40E or one of the end pieces of the filters 43 and 44.

In order to accommodate connector 41, shells 113 and 114 respectivelycomprise a cavity 41A and a cavity 41B.

Each of the channels 116A to 116F as well as each of the cavities 43Aand 44A is bordered on each side by a groove 50A to 50E serving toaccommodate a respective one of the beads 52A to 52E of the network ofbeads 51 shown in FIG. 8.

Each of the beads 52A to 52E of network 51 is slightly thicker than thedepth of grooves 50A to 50E such that the beads of network 51 eachproject from the reference surface 115.

Thus, along each of the channels 116A to 116F, 118A to 118F and alongthe cavities 43A, 44A, 43B and 44B, the films 125 and 126 are pinchedbetween a bead of network 51 and surface 117 of shell 114, when shells113 and 114 clamp bag 111.

This enables the pipes 112A to 112F to be delimited particularlyprecisely and to ensure fluid-tightness between films 125 and 126 alongthose pipes.

As a variant, beads 52A to 52E not only have a pinching function, butalso play the role of a heating device (here, electrical resistors)enabling the films 125 and 126 to be welded, in order to make thedelimitation of pipes 112A to 112F permanent.

To ensure that shells 113 and 114 are properly positioned relative toeach other in the closed state of press 110, shell 113 is provided ineach corner with a boss 55, here an outline of right-angled triangleform similar to that of the openings 42 of bag the 111, whereas shell114 is provided, at the corresponding locations, with cavities 56 ofcomplementary form to that of bosses 55.

To properly position bag 111, the operator takes care to engage thefilters 43 and 44 in the cavities 43A and 44A as well as to engage eachof the four bosses 55 in the corresponding opening 42 of bag 111.

The shaping of bag 111 by press 110 is carried out as for the shaping ofbag 11 by press 10.

Once bag 111 has been clamped between shells 113 and 114, the circuitformed by press 110 and bag 111 is ready to be placed in service.

It will be noted that in FIG. 7 the apertures 57A to 57D can be seen bywhich the distal end of sensors 121A to 121D can come into contactrespectively with pipe 112A (sensors 121A and 121B), pipe 112D (sensor121C) and pipe 112E (sensor 121D).

Similarly, in FIG. 9 the apertures 58A to 58G can be seen by which thefinger of the actuators 120A to 120G can come to respectively pinch pipe112A (actuators 120A and 120B), pipe 112B (actuator 120C), pipe 112D(actuator 120D), pipe 112E (actuators 120E and 120G), and pipe 112F(actuator 120F).

FIG. 6 diagrammatically shows the circuit 59 provided by press 110 andbag 111. On this circuit valves 60A to 60G are respectively formed bythe actuator 120A to 120G, by the pipe portion which the finger of thatactuator can pinch, and by the portion of shell 113 against which thepipe bears when it is pinched by the finger.

In the illustrated example, the inflation of bag 111 by injection of apneumatic agent through connector 41 has been made possible by the factthat each of the connectors 40A to 40E was obturated by a plug.

To place circuit 59 in service, these plugs are removed and connectors40A to 40E are connected to the rest of the installation for treatingbiological liquid of which circuit 59 is intended to form part.

In circuit 59, filter 43 is here a tangential flow filter (TFF) andfilter 44 is a final filter.

Connector 40A is provided to be connected to the delivery side of a feedpump, connector 40B to the delivery side of a transfer pump, connector40C to a connector of a feed bag of which another connector is connectedto the inlet side of the feed pump, connector 40D to the drain, andconnector 40E to a bag for collecting treated liquid.

Connector 40B serves to inject the liquid to treat into a loop formed bypipe 112E, by the feed bag connected to connector 40C, by the feed pumpof which the inlet side is connected to another connector of the feedbag and of which the delivery side is connected to connector 40A, bypipe 112A and by filter 43.

On injection of the liquid to treat by connector 40B, all the valves areopen, except for valves 60E and 60A.

Once the product to treat has been transferred into the feed bag, valves60F and 60C are closed, whereas the other valves are open and the feedpump is put into operation, such that the liquid to treat flows in theaforementioned loop.

On passage into filter 43, the product to treat is purified with theretentate passing into pipe 112E and the filtrate passing into pipe 112Dthen being evacuated to the drain.

When the liquid has sufficiently circulated in the loop and has attainedthe required characteristics of purity and concentration, its evacuationis performed to the collecting bag connected to connector 40E, bypassing valve 60B to the closed position and valve 60C to the openposition, the treated liquid thus attaining connector 40E by passing viafilter 44 where the liquid undergoes a final filtration.

It will be noted that the circuit 59 is capable of implementing, inaddition to the operations described above, various other operations byvirtue of the routing network formed by pipes 112A to 112F and by virtueof valves 60 to 60G which enable that network to adopt variousconfigurations.

Sensors 121A to 121B are all pressure sensors here. They enable theproper operation of the installation to be verified, and in particularto detect any occurrence of excess pressure (sensor 121A) and to ensureproper operation of filter 43 (sensors 121B to 121D).

FIGS. 10 to 19 illustrate a variant of shells 113 and 114 in whichgrooves 50A to 50E for the network 51 of beads 52A to 52E is provided onshell 114 rather than on shell 113; whereas the path of channels 116A to116F (shell 113) and 118A to 118F (shell 114) is arranged slightlydifferently, in particular in order to minimize the length of pipes 112Aand 112E.

In the drawings, shell 13, 13′ or 113′ is below shell 14 or 114.Consequently, in the present description, the shells are sometimesrespectively called lower shell and upper shell. However, there isnothing mandatory about this positioning and on the contrary shells 13,13′, 113 and 14, 114 may be disposed differently, for example with shell14, 114 below shell 13, 13′, 113 or else with the two shells disposedvertically rather than horizontally.

In the examples described above, the bag is inflated before beingclamped between the shells. In a variant not illustrated, the bag isfirst clamped between the shells before being inflated. Of course, inthis variant, the films such as 25, 125 and 26, 126 enlarge to conformto the recessed surfaces of the shells. In still another variant notillustrated, the bag is partially inflated before being clamped betweenthe shells and finally inflated after being clamped between the shells.

In variants that are not represented:

-   -   the circuit further includes a reservoir able to contain a        predetermined volume of liquid, for instance a reservoir        included in a loop having a filter with the filtrate evacuated        from the loop and the retentate remaining in the loop so as to        concentrate the fluid or a buffer reservoir for enabling a        physico-chemical value of the liquid such as the Ph to        stabilize;    -   instead of being unitary, the shells are formed by a set of        modular members associated together to delimit the different        portions of the circuit, with the modular members preferably        provided with marks or tags for ensuring that they are correctly        arranged relative to one another, the marks or tags being for        example written reference numbers or codes and/or wireless means        such as RFID tags;    -   the shells are of a material other than stainless steel, for        example of aluminum, plastic, ceramic or wood;    -   the shaping channels for the pipes comprised by the shells are        arranged differently, with, for example channels formed in only        one of the shells whereas in the other shell the surface for        contact with the bag is entirely planar; and/or the channels are        of a cross-section other than semi-circular, for example an oval        or U-shaped cross-section;    -   the complementary devices mounted on the shells are arranged        differently, are different from actuators for pinch valves or        from sensors of a physico-chemical value such as pressure, Ph or        temperature, or are even eliminated;    -   the films of the bag such as 11 or 111 are of a material other        than PureFlex™ film, for example in another film of several        layers compatible with biological liquids such as HyQ® CX5-14        film from the company Hyclone industries or Platinum UltraPack        film from the company Lonza;    -   the operation of injecting an inflating agent at higher pressure        than atmospheric pressure is replaced by the suction of the        faces of the bag such as 11 or 111 by the faces in contact of        the shell, the injection of the inflating agent then        corresponding to the mere entry of air into the bag which        consequently occurs; and/or the injection of the inflating agent        is carried out at the same time by suction at the shells and by        injection of an inflating agent at higher pressure than        atmospheric pressure (of course, suction by the shells is        carried out by virtue of the presence thereon of channels        opening on the face provided to be in contact with the bag,        those channels being linked to a vacuum source);    -   the inflating agent injected by the connector such as 41 is        different from a pneumatic agent, for example water or another        liquid inflating agent; and/or there is more than one inflating        connector or that connector is eliminated with the inflating        agent being injected by one of the routing network connectors;    -   the pipes of the bag such as 11 or 111, rather than being        totally inexistent at the initial state of the bag, are        partially preformed; and/or    -   the circuit formed is different from the circuit 59 with, for        example, a number of pipes, of connectors and of filters        different, for example a single filter, or even no filter, for        example to perform a chromatography operation.

Numerous other variants are possible according to circumstances, and inthis connection it is to be noted that the invention is not limited tothe examples described and shown.

The invention claimed is:
 1. A method comprising: providing a circuitfor routing biological liquid, the circuit comprising a press, adisposable bag, routing network connectors, and a routing network forrouting the liquid between said connectors, the circuit being formed bysteps of: providing the disposable bag as two flexible films attachedtogether by a seal delimiting a closed contour with said routing networkconnectors and an inflating connector, said routing network connectorsand said inflating connector each opening respectively inside of saidclosed contour and outside of said closed contour; providing the pressas two shells, said shells each comprising at least one recessedchannel; and forming pipes of said routing network between said films byclamping said bag between said shells and by injecting a pneumaticinflating agent into said bag clamped between said shells via saidinflating connector, said bag and said press being configured such thatat least one of said pipes has a contour of which at least one portionis delimited exclusively by cooperation with said press, the portion ofthe contour of the at least one pipe which is delimited exclusively bycooperation with the press including contact zones between the films,said contact zones bordering said at least one pipe and beingfluid-tight, and said injecting causing said pipes to each be formedinto conformity with opposing recessed channels of the two shells todefine said contour of which at least one portion is delimitedexclusively by cooperation with said press; wherein said circuit canonly be used while said bag remains clamped between said shells.
 2. Amethod according to claim 1, wherein said inflating connector isseparate from said routing network connectors.
 3. A method according toclaim 1 or 2, wherein the step of forming said pipes comprises beginningthe step of injecting said inflating agent before said clamping of saidbag between said shells.
 4. A method according to claim 3, wherein thestep of injecting said inflating agent is preceded by pre-closing saidpress while said bag is in immediate proximity to each of the twoshells.
 5. A method according to claim 1, wherein each of said recessedchannels has a semi-circular cross-section.
 6. A method according toclaim 1, wherein the press comprises actuators of pinch valves andsensors of a physico-chemical value.
 7. A method according to claim 6,wherein the actuators each comprise a body attached to one of saidshells and a moveable finger capable of adopting a retracted positionand a working position projecting from a respective recesses channel. 8.A method according to claim 7, wherein each actuator enables one of saidpipes to be pinched between said moveable finger to allow or prevent thepassage of liquid at that location.
 9. A method according to claim 6,wherein the sensors each comprise a body attached to one of said shellsin register with a respective recessed channel, a distal end of the bodyopening into the respective recessed channel.
 10. A method according toclaim 9, wherein said physico-chemical value is a temperature orpressure which can be measured by contact of the distal end with arespective pipe without contacting fluid running through the respectivepipe.
 11. A method according to claim 1, wherein said shells are eachformed from stainless steel and are each of a generally parallelepipedshape.
 12. A method according to claim 1, wherein the seal delimitingthe closed contour is formed at a periphery of the films.
 13. A methodaccording to claim 1, further comprising providing obturating plugs oneach of the routing network connectors and on the inflating connectorand sterilizing the bag by gamma irradiation.
 14. A method according toclaim 1, wherein said pneumatic inflating agent is compressed airpurified through an hydrophobic filter.
 15. A method according to claim1, wherein said pipes of the routing network are not pre-formed in thebags prior to said forming.
 16. A method according to claim 1, whereineach said recessed channel is bordered on each side by a groove in whichis accommodated a respective bead of a network of beads serving to applysaid flexible films against each other along said pipes.
 17. A methodaccording to claim 1, further comprising a filter enclosed within saiddisposable bag.